The Efficacy of Two Intravenous Sedative Drugs in Management of Uncooperative Children for Dental Treatments.

STATEMENT OF THE PROBLEM
Some children do not show an appropriate cooperation with their dentist. A number of them cannot be managed by local anesthesia and the usual techniques used to control behaviors, so further steps are required to control their pain and anxiety. Pharmaceutical control is recommended through sedation or general anesthesia.


PURPOSE
This study was aimed to evaluate two groups of drugs in intravenous sedation method.


MATERIALS AND METHOD
In this clinical trial intervention study, patients were randomly divided into two groups of 18 and 20 and each group received either intravenous midazolam-ketamine or midazolam-fentanyl. During the procedure, 0.25mg midazolam was administered to both groups if needed. The scores of intraoperative sedation and operation conditions were evaluated and recorded by dental sedation teacher groups (DSTG) system in the 10(th), 20(th), 30(th) and 40(th) minutes of the operation. The results were analyzed by SPSS (version 16) using independent T-test, Wilcoxon, Mann-Whitney and Pearson Chi-Square tests as appropriated.


RESULTS
There was no significant difference between the two groups in sedation period (p= 0.55), recovery time (p= 0.18), Frankl score (p= 0.83(, score of intraoperative sedation and operating conditions (p> 0.05), and sedation complications (p= 0.612). In addition, no complication occurred in recovery.


CONCLUSION
There was no significant difference between the two drug groups; both were appropriate in controlling children's behavior.


Introduction
Dental treatments seem painful to most children. [1] In many cases, this might cause the children to avoid necessary dental treatments or to tolerate it with great fear. [2][3] Eliminating negative memories of dentistry is important for children and is possible through sedation, and it induces positive attitude towards treatment with medications and other different methods. In this case, depending on the drug type and depth of sedation, the patient forgets a part or all of the treatment and nothing will be remembered after the treatment.
One of the methods to manage children in dental procedures is conscious sedation, during which the child would be sedated by use of sedative or anesthetic drugs, but is still able to cooperate with the dentist and respond to verbal commands. The patient's comfort throughout the procedure and forgetting the events are among the characteristics of sedation. Using midazolam in dentistry is very acceptable and common and its forgetting effects are recognized in the literature. [4][5] Three most commonly used sedation roots are inhalational, oral and intravenous. Although particular dosages of drug are recommended for conscious sedation in the mentioned techniques, usually none of these methods would cause an unarousable sleep, the reason they are named as conscious sedation. [6][7] In intravenous method, the drugs that are used for conscious sedation are directly administered to venous blood through the veins. Conscious sedation causes the patient not to remember much of what happened during the procedure and after it is done. [8] Benzodiazepines, ketamine, opioids, and propofol are the medications used in intravenous sedation. Based on the study by Nadin et al. (1997), midazolam caused anterograde amnesia in most patients. [9] A study by Azevedo et al. (2013) proved midazolam (in the studied dosage) to be an effective and innocuous medication for pediatric sedation. [10] Ketamine is a non-barbiturate drug derived from phencyclidine; [11] it may be necessary to be combined with benzodiazepines in order to restrict the arousing reactions as well as enhancing the amnesia. Ketamine can result in significant but transient increase of systemic blood pressure, heart rate, and cardiac output through mediated stimulation of central sympathetic. Such effects can be adjusted by concurrent administration of benzodiazepines, opioids, or inhalational anesthetics. [6,8,[12][13] Okamoto et al. (1992) found that ketamine dosage would considerably decrease when used in combination with benzodiazepine. [14] Damle et al. On the operation day, the anesthesiologist randomly allocated the patients in one of the two groups, gave them an injection of the required drugs with respect to their weight, and managed the patient throughout the operation. Neither the dentist nor the person who was collecting data had a clue about the grouping method.
After completing the sampling, the related codes were removed. The first group received intravenous midazolam (0.05mg/kg) and ketamine (0.5mg/kg), the second group intravenous midazolam (0.05mg/kg) and fentanyl (0.5µg/kg), both within a 2-minute time interval.
Throughout the operation, midazolam (0.25mg) was administered to both groups if needed and the efficacy of both drug groups was evaluated in managing the children during the dental operation and after it. In addition, the side effects of the drugs were checked including restlessness, fear of injection, nausea and vomiting, complications of sedation and recovery, sedation period, and recovery period. Dental sedation teacher groups (DSTG) system [17] was used to assess the scores of intraoperative sedation .The operating condition in each 10-minute intervals from the beginning of operation (10,20,30, and 40 minutes from the start), as well as the data obtained through Frankl behavioral rating scale [18] concerning the ability to complete the dental treatment were all recorded on a sheet.
After the operation was over, the patient was subjected to standard care in recovery and was released when meeting the discharge conditions, and received comprehensive instructions thereafter. Throughout the operation, the patient was supervised by anesthesiologist and the vital signs and oxygen saturation was checked by using a pulse oximeter. The dentist administered local anesthesia according to the pediatric dentistry protocol. The results were analyzed by SPSS (version 16) using independent T-test, Wilcoxon, Mann-Whitney, and Pearson Chi-square tests as appropriated.

Results
In this study, 38 patients were evaluated in two groups;   (Table 1).
Using Mann-Whitney test, no significant difference was detected between the two groups concerning the score of intraoperative sedation and the score of     (Table 3).

Midazolam-Fentanyl
Wilcoxon test revealed significant difference between the score of sedation in the two groups of midazolam-ketamine and midazolam-fentanyl in the 10-20, 10-30 and 10-40 minutes of the operation (p< 0.05).
There was also significant difference between the score of operating conditions in the two groups over the 10-20, 10-30, 20-40 and 30-40 minutes of the operation (p< 0.05). Neither group showed recovery complications, so no significant difference were found between the groups concerning the recovery complications.

Discussion
Sedative drugs are used in pediatric dentistry to help managing the children behavior during the treatment procedure. They are expected to have the children change their behavior and take the sequential dental treatments with appropriate cooperation without using such medications. [19][20][21] In this study, the mean seda- In a study enrolled by Milnes et al. (2000), no complication was detected throughout the operation and recovery in children who received intravenous midazolam-nalbuphine-droperidol. [22] In the current study, during dental treatment in midazolam-ketamine group 3,   and found that sedation score in 0.75 and 1mg/kg midazolam groups were higher than 0.5mg/kg group. [23] Comparing the score of operating conditions, no

Conclusion
There existed no significant difference between the two groups of midazolam-ketamine and midazolam-fentanyl in terms of sedation complications, recovery complications, Frankl score, sedation ,and recovery period, as well as score of intraoperative sedation, operating conditions during the 10 th , 20 th , 30 th , and 40 minutes of operation, gender, and age. Both groups provided sufficient score of intraoperative sedation until the 30 th minute, and ideal operating conditions until the 20 th minute of the operation. Hence, until the 20 th minute of the procedure, drugs can be suitable for managing the children, neither was superior and each one was effective per se.
Therefore, it seems that it makes no difference to combine midazolam with ketamine or fentanyl.